CADASIL, Cerebral Autosomal Dominant Arteriopatie With Subcortical Infarcts and Leukoencephalopathy
Conditions
Keywords
CADASIL, NOTCH3, Stroke, Cerebral Small Vessel Disease, Prospective Study, Korea
Brief summary
K-CADASIL is a 10-year prospective study of 500 Korean patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic brain disease that causes stroke and dementia. The investigators will track symptoms, brain scans, memory tests, and gene information to understand disease progression in Koreans and identify better treatments. Participants will visit clinics regularly for check-ups and blood tests. This study aims to help improve care for CADASIL patients and families worldwide.
Detailed description
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant small vessel disease caused by mutations in the NOTCH3 gene located on chromosome 19, leading to progressive involvement of small cerebral arteries. Clinical manifestations of CADASIL vary across populations. Unlike European patients, those from East Asia, including Korea, often show distinct genotypes, neuroimaging features, and clinical phenotypes. To date, no large multicenter study has comprehensively described the clinical, genetic, and imaging characteristics of Korean patients with CADASIL. Furthermore, long-term prognostic data are lacking. It remains unclear how vascular comorbidities and their management influence disease progression and outcomes in this population. The K-CADASIL study is designed as a nationwide, multicenter, prospective observational cohort enrolling approximately 500 Korean patients with CADASIL. Participants will be followed for 10 years, undergoing regular clinical evaluations, laboratory testing, neuropsychological assessments, and magnetic resonance imaging (MRI). The primary goals of this study are to: (1) characterize the clinical, genetic, and neuroimaging features of Korean CADASIL patients, (2) investigate long-term prognosis and identify factors influencing disease outcomes, and (3) establish a genomic and proteomic biorepository to enable future multi-omics analyses exploring the molecular determinants of disease development and prognosis.
Interventions
None listed
Sponsors
Jeju National University Hospital
Asan Medical Center
Chonnam National University Hospital
Chungbuk National University Hospital
Dong-A University Hospital
Ewha Woman University Medical Center
Hallym University Medical Center
Hanyang University Seoul Hospital
Inje University Ilsan Paik Hospital
Kangdong Sacred Heart Hospital
Keimyung University Dongsan Medical Center
Korea University Ansan Hospital
Korea University Guro Hospital
Kyung Hee University Hospital
Kyungpook National University Hospital
Nowon Eulji Medical Center
Pusan National University Hospital
Seoul Medical Center
Seoul National University Bundang Hospital
Seoul National University Hospital
Severance Hospital
Soonchunhyang University Hospital
Ulsan University Hospital
Yeungnam University Hospital
Daejeon Eulji University Medical Center
Jeonbuk National University Hospital
DongGuk University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 19 years * CADASIL suspected or confirmed by genetic testing (NOTCH3 mutation) * Able to provide written informed consent (participant or legally authorized representative)
Exclusion criteria
* Contraindication to MRI (claustrophobia, metal implants, pacemaker) * Acute ischemic or hemorrhagic stroke within 180 days prior to enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| New-onset stroke events | 10 years from enrollment | Number of Participants with New-onset Stroke Events, Date of Occurrence, Subtype, Location, and National Institutes of Health Stroke Scale \[NIHSS\] Score. |
| New-onset mild cognitive impairment (MCI) or dementia | 10 years from enrollment | Number of Participants with New-onset MCI or Dementia, Date of Onset, and Dementia Subtype (Alzheimer Disease Dementia, Vascular Dementia, Mixed Dementia) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cerebral small vessel disease burden on MRI | Baseline, 3 years, 6 years | Periventricular White Matter Hyperintensity (WMH) Fazekas Scale (0-3; higher scores indicate greater severity), Deep WMH Fazekas Scale (0-3; higher scores indicate greater severity), Number of Lacunes, Number of Cerebral Microbleeds, Normalized White Matter Hyperintensity (nWMH) Volume (%) |
| Cognitive function composite score changes | Baseline, 3 years, 6 years | Korean-Trail Making Test-Elderly's Version (K-TMT-E) Standard Score (higher scores indicate better performance), Korean-Mini Mental State Examination (K-MMSE) Standard Score (0-30; higher scores indicate better cognitive function), Clinical Dementia Rating (CDR) Global Score (0-3; higher scores indicate worse dementia severity), Korean version Montreal Cognitive Assessment (K-MoCA) Score (0-30; higher scores indicate better cognitive function) |
Countries
South Korea
Contacts
CONTACTJay Chol Professor Choi, MD, PhD, MD, PhD
Outcome results
None listed